Hollow viscous and soild organ tonometry

ABSTRACT

Ischemia in a hollow internal organ can be detected in its incipient stages by obtaining a CO 2  sample from within the organ of interest, measuring the partial pressure of CO 2  sample, measuring the bicarbonate concentration of an arterial blood sample, and on the basis of these two measurements calculating the pH of the wall of the organ. The value of the pH is an indicator of the onset of ischemia in the organ. The CO 2  sample is obtained by a novel catheter, multiple embodiments of which are disclosed. Also disclosed is a method for determining the vitality or adequacy of oxygenation of the whole body, or a solid internal organ, by the measurement of the pH of venous blood.

This is a continuation of U.S. patent application Ser. No. 08/279,000,filed Jul. 22, 1994, now abandoned, which is continuation of 08/034,596,filed Mar. 22, 1993, now abandoned, which is a continuation of07/719,097, filed Jun. 20, 1991, now abandoned, which is a continuationof 07/513,026, filed Apr. 24, 1990 (now abandoned), which is acontinuation of 07/237,286, filed Aug. 26, 1988 (now abandoned), whichis a continuation-in-part of 08/233,888, filed Aug. 17, 1988 (nowabandoned), which is a continuation of 07/120,720, filed Nov. 6, 1987(now abandoned), which is a continuation of 07/013,552, filed Feb. 11,1987 (now abandoned), which is a continuation of 06/833,287, filed Feb.27, 1986 (now U.S. Pat. No. 4,643,192), which is a continuation of06/360,718, filed Mar. 22, 1982 (now abandoned).

BACKGROUND AND SUMMARY OF THE INVENTION

This invention relates to medical diagnostic equipment and methods andis particularly concerned with hollow viscus tonometry, as well asdetermining the vitality or adequacy of oxygenation of the body or solidinternal body organs.

Stress ulceration and intestinal ischemia are two serious problems thatplague physicians involved in the management of patients in intensivecare units. Intestinal ischemia, in particular, has an insidious onsetand may not be detected until days after the intestine has becomegangrenous. A delay in the diagnosis of intestinal ischemia may havedevastating consequences for a patient. The availability of means forearly diagnosis and management of patients with these problems wouldhave immediate applicability in all intensive care units, especiallywhere the procedure can be conveniently conducted with reasonable safetyand reliability.

It has been established that a fall in the intramuscosal pH may precedethe development of stress ulceration. One aspect of the inventioninvolves the discovery, in the laboratory, that a fall in intrasmucosalpH also occurs within minutes of inducing intestinal ischemia in dogs.The fall in pH in intestinal mucosal, and hence the liklihood of stressulceration or ischemia, can be reliably calculated from a pCO₂ (partialpressure of CO₂) in luminal fluid and the bicarbonate concentration inarterial blood. The method of calculating the pH in intestinal muscosaltissue, pursuant to principles of the invention, has been validated bydirect measurements under a variety of conditions simulating clinicalproblems. A correlation coefficient in the order of 0.92 to 0.95 hasbeen obtained in each of sixteen dogs. It will be readily recognizedthat the validity of the procedure is inherently extensible to humans.

To measure the pCO₂ in the lumen of the gut it is necessary to obtain asample of fluid that has been in contact with the wall of the gut for acertain time period, usually at least half an hour. It is difficult toaspirate fluid from the lumen of the gut with any consistency, for anyfluid instilled into the lumen passes into distal and proximal regions.It is much easier to obtain samples from the stomach, but samplesobtained from the stomach frequently contain foreign material that candamage a gas analyzer.

A particular aspect of the invention involves the creation of a new andunique catheter via which the desired sample or samples can be obtainedwithout the complications of prior techniques. One embodiment of the newand unique catheter comprises a catheter tube having a walled samplingchamber on the tube with the sampling chamber being in communicationwith the hollow interior of the tube. The wall of the sampling chambercomprises a material which is substantially impermeable to liquid yet ishighly permeable to gas. One suitable material is polydimethylsiloxaneelastomer.

In use the catheter is introduced into a patient to place the samplingchamber at a desired site within the organ of interest. An aspiratingliquid fills the interior of the sampling chamber. The sampling chamberis left in place at the desired sampling site long enough to allow thegases present to diffuse through the wall of the sampling chamber intothe aspirating liquid. The time should be long enough for the gases toequilibrate. The liquid impermeable nature of the sampling chamber wallmaterial prevents both the aspirating liquid from leaking out of thechamber and also the intrusion of any liquids into the aspiratingliquid. After the appropriate amount of placement time has elapsed theaspirating liquid is aspirated along with the gases which have diffusedinto it. The sample thus obtained is analyzed for gas content, inparticular for pCO₂. In this way the pCO₂ within the lumen of the gutcan be reliably measured with the fluid being free from lumenal debris.

In carrying out the diagnostic method of the invention the pCO₂measurement is utilized in conjunction with a measurement of thebicarbonate concentration in an arterial blood sample of the patient fordetermining the pH of the tract wall.

Depending upon the particular condition of a given patient, the cathetermay be left in place and samples may be taken at periodic intervals sothat pH values may be periodically calculated. The procedure has a highreliability in accurately diagnosing intestinal ischemia in itsincipient stages and such detection can be useful in treating thepatient so that the potentially devastating consequences resulting fromless timely detection may often be avoided.

The invention has applicability to many hollow internal organs althoughin the techniques described in detail herein the invention involvesdiagnosis within the gastrointestinal tract system. Depending upon theparticular site or sites of interest within a patient, different typesof catheters embodying principles of the invention may be appropriatelyused. One embodiment involves a catheter as described above. In thatembodiment the catheter has a single sampling chamber and a singlewalled tube. Another embodiment contemplates the use of multipleindividual single sampling chamber catheters of varying lengths bundledtogether to form a multiple sampling site catheter. Still anotherembodiment involves the use of a sump-type nasogastric tube. Yet anotherembodiment comprises a pliable catheter with a mercury bag at its endwhich may be used for certain procedures. In use of an embodiment thatemploys multiple sampling chambers, the pH in intestinal mucosal tissueat one site may be calculated and compared with the calculated pH valuesat other sites. This analysis can be a useful diagnostic aid to theattending physician. In the case of an abdominal aortic resection amultiple sampling chamber type catheter may be placed intralumenally inseries in the colon at the time of the resection, and it may be used toaid in the early detection of colonic ischemia that occurs insidiouslyin approximately five percent of the patients subjected to this majoroperation. A multiple sampling chamber embodiment may also be introducedinto the small intestine to monitor the pH and hence perfusion of thegut in patients with low flow states. In critically ill patients whorequire a nasogastric tube, a single sampling chamber embodiment may beincorporated into a conventional nasogastric tube and placed in thepatient's stomach.

It is further contemplated that the invention may be practiced inconnection with diagnosis of the biliary tract, urinary tract andpancreas for monitoring pH and hence perfusion of the associated organs.

In connection with this invention, a preliminary novelty searchdeveloped the following U.S. Pat. Nos. 2,470,665; 3,227,154; 3,548,805;3,572,315; 3,952,730; and 4,168,703, none of which are deemed pertinentto the claims of the present invention.

The foregoing features and benefits of the invention in its severalaspects, along with additional features and benefits, will be seen inthe ensuing description and claims which should be considered inconjunction with the accompanying drawings. The drawings disclosepresently preferred embodiments of catheters which embody principles ofthe invention and are used in the diagnostic aspects of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagrammatic view of a catheter embodying principles of theinvention.

FIG. 2 is another embodiment of catheter embodying principles of theinvention.

FIG. 3 is yet another embodiment of catheter embodying principles of theinvention.

FIG. 4 is still another embodiment of catheter embodying principles ofthe invention;

FIG. 5 is a detailed view illustrating the tonometric catheter of FIG. 1in use within the stomach;

FIG. 6 is a detailed view illustrating the tonometric catheter in usewithin the colon.

DESCRIPTION OF THE PREFERRED EMBODIMENT

FIG. 1 illustrates a first embodiment of catheter 10. The cathetercomprises a length of suitable tubing 12 one end 14 of which is closed,and the opposite end of which contains a connector such as a luer-lock16 or equivalent. A sampling chamber 18 is provided on the tube adjacentthe closed end 14.

The illustrated embodiment utilizes a tubular element 18a forming thesampling chamber wall. The preferred form of tubular element ispolydemethylsiloxane elastomer. The tubular element has an internaldiameter which allows it to be fitted over the tubing 12. The axial andsegments of the tubular element 18a are secured to the outer wall oftube 12 at the locations indicated by the reference numerals 20 and 22.The attachment may be made in any suitable fashion with adhesive being asuitable attachment medium. Thus, the ends of the tubular element 18aare sealed in a closed relationship to the outer wall of the tube 12thereby forming the sampling chamber 18 adjacent tube end 14. The wallmaterial of the sampling chamber has a certain elasticity so as to allowthe enclosure to assume a slightly ballooned or ovoidal shape whenfilled by aspirating liquid, as will be explained hereinafter.

Before the tubular element 18a is inserted over tube 12, suitableapertures 24 (shown on an enlarged scale in the drawing) are provided inthe wall of tube 12 so that after assembly of the tubular element 18athe tube 12 the apertures 24 provide communication between the interiorof tube 12 and the interior of the sampling chamber 18.

The material of the tubular element 18a possesses a characteristicwhereby it is poorly permeable to liquid fluid while it is freelypermeable to gaseous fluid. This property is important in practice ofthe invention. The material is also substantially impervious to thecontents of the intestinal tract.

In one form of use the catheter is introduced into a patient by beingfed into the colon from the anus and positioned intraoperatively. Asuitable aspirating fluid, such as a saline solution, is introduced viathe luer-lock 16, tube 12, and apertures 24 to fill the interior of thesampling chamber. The fluid passes through the apertures 24 filling theinterior of the sampling chamber such that the sampling chamber assumesa balloon-like state.

According to the method of the invention the catheter is placed suchthat the sampling chamber is at a desired sampling site in the internalorgan of interest. It is left at this site for a sufficient amount oftime to allow gases, carbon dioxide being the particular gas ofinterest, to diffuse across the wall of the chamber into the aspiratingliquid. Desirably the length of time should be sufficient to allow thegases to equilibrate. For example, one half hour may be suitable incertain applications.

The aspirating liquid containing the carbon dioxide gas is thenwithdrawn via the luer end lock 16. The aspirated sample thus obtainedis subjected to analysis by a conventional gas analyzer to measure thepCO₂ content of the lumenal fluid. A measurement of the bicarbonateconcentration in the arterial blood of the patient is also obtained.These two measurements are then used to calculate the pH of the tract.Measurements may be taken at periodic intervals in the same manner andin this way a record of pH values can be established.

The invention, in one respect, involves recognition of the principlethat the partial pressure of gas in the lumen of the gastrointestinaltract is the same or very close to that in the wall of thegastrointestinal tract under a steady state condition and hence, can beused as a measure of the partial pressure of gas, especially CO₂, in thewall of that part of the gastrointestinal tract. The pH in the wall ofthe gastrointestinal tract can be calculated from this value if thebicarbonate concentration in arterial blood is also known. With thecatheter of the invention the partial pressure of gas within thegastrointestinal tract can be readily measured because it allows a clearfluid sample, free of objectionable particulates and the like, to beobtained.

As explained earlier, a drop in the intramucosal pH has been found toaccompany development of intestinal ischemia, and therefore the pHmonitoring can be used to monitor four the incipiency of thispotentially devastating condition. The earlier warning obtained with theinvention offers the possibility of earlier treatment to counteract thecondition.

FIG. 2 illustrates a further embodiment of the catheter 30. Thisembodiment is also useful in the colon. The catheter 30 comprisesmultiple sampling chambers 18 at spaced locations along the length ofthe catheter. In this regard the catheter 30 is constructed as a bundleof individual catheters, such as the catheter 10 of FIG. 1, theindividual catheters having various lengths. The illustrated example hasfive sampling chambers. This allows measurements to be taken at fivedifferent sites within the organ of interest and is useful formonitoring pH values not only in time at a particular sampling site butalso in respect to concurrent pH measurements at different sites.

FIG. 3 illustrates a further embodiment of catheter 40 which comprises atube 18a forming the wall of the sampling chamber; however, the tube 42comprises a conventional double lumen nasogastric sump tube with a thirdlumen for the sampling chamber 18. The air and aspiration ports 44, 46are of the nasogastric tube and the luer-end lock 16 is for the thirdlumen which leads to the sampling chamber 18. The catheter 40 isintended for use in the stomach. In this regard the catheter may beinserted into a patient in the same manner as a nasogastric tube, andthe aspirating fluid for obtaining the CO₂ measurement is introduced andaspirated via luer lock 16 in the same manner as that for the previouslydescribed catheters.

FIG. 4 illustrates a still further embodiment of catheter 50 which isthe same as the embodiment 10 of FIG. 1 except that the end 14 includesa sealed mercury bag 52. This catheter is intended for use in the smallintestine, and it should be very soft and pliable with the mercury bagallowing peristalsis to position the tube in the small intestine. Itshould be long enough to reach the terminal ileum, and the same lengthas a colonscope would be more than adequate.

If desired, any of the embodiments of single catheter may be bundledtogether as in the manner of FIG. 2 so as to provide multiple samplingsites in any catheter construction.

Desirably the volume of the sampling chamber should be relatively smallin order to facilitate rapid equilibration of gas yet it must be largeenough so that a suitable sample of about one milliliter for use in thegas analyzer can be withdrawn via the element 16. For example, aroundtwo milliliters is a suitable volume. The tubes such as the tube 12should be of small caliber to insure as small a dead space as possiblewithin the patient when in use. Tube 12 should also have as small afluid volume (say about two-tenths milliliter) so that a minimum ofaspirating liquid need be withdrawn at element 16 in advance of thesample from the chamber 18. The tube wall 12 should also be impermeableto gas. The luer end locks are conventional for connection to a syringewhen aspirating fluid is to be introduced or withdrawn. The cathetersmay also contain rapid opaque markers for use in verifying position ofthe sampling chambers in the gut.

Where the catheter is to be left in the lumen of the gut for an extendedperiod of time, for example several days, it should be soft enough to beallowed to remain in this position without damage to the wall of thegut. To facilitate insertion, for example into the colon, the cathetershould be firm enough to allow for proper feeding. In this regard it maybe appropriate to use a wire stent during insertion to facilitatepositioning of the catheter with the wire stent being removed afterproper positioning has been obtained.

While the preferred embodiment has been disclosed in connection withmonitoring of the gastrointestinal tract it will be appreciated that itsprinciples are applicable to other hollow internal organs to monitor pHand hence perfusion of those organs. Also while a preferred detailedconstruction for a catheter, such as described in FIG. 1, has beendisclosed, it will be appreciated that other constructions may bedeveloped which are equally as suitable. The disclosed constructionhowever is presently preferred for the reason that it is readilyfabricated using existing available materials. Other embodiments mayinclude other, but equivalent materials for the sampling chamber wall.They may also differ in the specific fabrication details. As an example,the sampling chamber may be eccentric rather than symmetric about thetube 12.

It has now been further discovered that the pH of venous blood providesan excellent measure of the adequacy of tissue oxygenation of the wholebody or organs, including solid organs, comparable to that achieved inhollow viscus organs by the method described herein, as well as thatdescribed in my co-pending and commonly assigned applications filed ofeven date herewith that relate to the use of a tonometric catheter todetermine the adequacy of tissue oxygenation via the measurement of thepH of the wall of a hollow, viscus organ. See my co-pending and commonlyassigned applications, previously filed entitled "Remote SensingTonometric Catheter Apparatus and Method" and "Tonometric CatheterCombination", bearing respective Ser. Nos. 237,287 filed Aug. 26, 1988(now abandoned), and 237,286, filed Aug. 26, 1988 (now abandoned); bothcompletely and expressly incorporated herein by reference in toto.

For example, the methods of the present invention include the measure ofthe adequacy of whole-body oxygenation by measuring the pH of a centralvenous location. This may be done by tonometric sampling, or by theinsertion of an electronic sensing means for measuring a fluid or gasproperty of the venous blood indicative of pH, or pH itself. This wouldinclude such means as a pH, pCO₂ or pO₂ electronic sensing means, suchas a probe, placed into a central venous location. A tonometric catheterwhich includes a sampling chamber may also be employed. The samplingchamber is preferably constructed such that at least a portion of it ispermeable to a gas or fluid property indicative of the pH of the venousblood in which it is placed. The sampling chamber of a tonometriccatheter should also be impermeable to other materials that mayinterfere with the measurement of the desired gas or fluid property,such as other gases, proteins and the like. In a highly preferredembodiment, an ion-selective membrane is employed. The sampling chambermay optionally include a first non-temperature sensing means, and asecond temperature sensing means, both in communication with saidsampling chamber.

When no sensing means is employed, the tonometric catheter preferablyemploys a walled tonometric lumen, and said sampling chamber is incommunication with said lumen. This provides the ability to carry outthe aspiration of the sampling fluid or medium that is necessary when noremote sensing means is employed.

This method overcomes the problems associated with current methods ofmeasuring whole-body oxygenation. Most methods currently employed todetermine whole-body oxygenation include costly, time-consuming anderror-prone measurements that typically include whole-body oxygenconsumption and oxygen delivery. Another somewhat unreliable methodcurrently employed is the frequently unreliable measurement of oxygensaturation in central venous blood.

The present method employing a central venous pH measurement overcomesmany of the disadvantages of the currently art-employed methods; it hasthe additional advantage of being extremely reliable and relativelyinexpensive.

This method is also useful in measuring the vitality or adequacy oftissue oxygenation for a specific solid internal organ, such as thebrain, liver, kidney, or a limb, by measuring the pH of a venous vesseldraining that organ or limb.

The insertion of a pH, pO₂ or pCO₂ catheter in the jugular, hepatic orrenal veins, or any other regional vein draining a limb or the kidney,can be employed to measure the adequacy of tissue oxygenation inregional solid organs. A pH catheter and measurement is highlypreferred.

Measurement of the adequacy of tissue oxygenation in the brain by themethods of the present invention is of particular interest because ofthe current lack of any art-disclosed or art-employed non-invasive, orminimally invasive, method of monitoring the adequacy of tissueoxygenation in this organ. The importance and significance of being ableto make this measurement reliably and with minimum invasiveness andcost, especially in patient populations such as the elderly, patientshaving carotid artery surgery or patients with head trauma, with areliable method cannot be over estimated.

In employing the methods of the present invention, the catheter may beinserted, for example, percutaneously into a jugular vein and advancedto monitor the venous drainage from the brain with great ease andminimal risk. Many patients in need of such measurements already have acatheter in the jugular vein for other non-pH central venousmeasurements. Other methods currently employed in clinical setting usedto measure vitality of the brain, or the adequacy of its oxygenation orthat of its tissue, include (1) EEG measurements which are cumbersome,difficult to interpret, and subject to electrical interference; (2)near-infrared-spectroscopy, which is costly, cumbersome and currentlyonly applicable to neonates or premature babies with uncalcified skulls;(3) the Richmond-bolt, which requires that a hole be drilled into theskull and only measures pressure, thus providing no information aboutthe adequacy of tissue oxygenation; and (4) NMR or nuclear magneticresonance, which is still somewhat experimental, extremely costly anddifficult to interpret. None of the above methods provide the preciseinformation required to determine whether tissue oxygenation of thebrain is adequate.

Measurement of the adequacy of tissue oxygenation in the liver is alsoof particular interest because of the importance of the liver inmetabolizing drugs; the disturbance in drug metabolism precipitated bydisturbances in hepatic perfusion; and because of the increasingfrequency of liver transplants. For example, the measurements of pH inhepatic venous blood according to the instant invention provides aprecise, reliable and relatively inexpensive method of monitoring theadequacy of hepatic oxygenation in all patents who are critically ill,including those having liver transplants. Other techniques that attemptto measure the vitality of adequacy of oxygenation of the liver includeopen biopsy of the liver. Some work has been attempted which involvesintrahepatic tissue pH probes. The problem with tissue pH probes is theartefact created by the invasive insertion of the probe, and thedifficulty of probe placement and of maintaining its position in theliver tissue as the liver moves with respiration. Measurements ofhepatic venous pH according to the methods of the present invention donot have these shortcomings.

Accordingly, the present invention relates to a method for determiningthe vitality or adequacy of whole-body oxygenation of a human or othermammal in vivo comprising:

(i) providing a means for measuring a fluid or gas property indicativeof pH, such as an arterial pH catheter, suitable for insertion into acentral venous location;

(ii) inserting said means such as a pH catheter into a central venouslocation;

(iii) measuring the pH of the blood at said central venous locationeither directly or from the selected fluid or gas property; and

(iv) determining the vitality or adequacy of whole-body oxygenation ofsaid human or mammal from said pH measurement.

This method may also be employed to determine the vitality or adequacyof oxygenation of a solid internal organ. It therefore comprises thesteps of:

(i) providing a means for measuring a fluid or gas property indicativeof pH, such as an arterial pH catheter, suitable for insertion into avenous vessel at least partially draining an organ of interest;

(ii) inserting said means or catheter into said venous vessel drainingsaid organ;

(iii) measuring the pH of the blood in said venous vessel, eitherdirectly or from the selected fluid or gas property; and

(iv) determining the vitality or adequacy of oxygenation of said organfrom said pH measurement.

While a preferred embodiment of the invention has been disclosed, itwill be appreciated that principles of the invention, as set forth inthe following claims, are applicable to other embodiments.

What is claimed is:
 1. A tonometric catheter device for detecting theonset of ischemia in a hollow internal organ, comprising a catheterhaving a catheter tube; a walled sampling chamber on the tube incommunication with the interior of the tube, said walled samplingchamber being defined by a balloon member generally surrounding aportion of said catheter tube and sealingly interconnected therewith,the wall of said walled sampling chamber being composed of a deformablematerial which is freely permeable to one or more liquid fluids orgaseous fluids of interest, said fluids of interest including oxygengases and carbon dioxide in solution, but poorly permeable to otherfluids; means for introducing said catheter into the hollow internalorgan, said balloon member being inflated for forming an interior spacebetween said balloon member and said catheter tube for selectivelypositioning a portion of said balloon member substantially in contactwith a wall portion of the internal organ at a desired sampling sitetherein in order to allow said fluids of interest to permeate from thetissue of the wall portion of the organ into said sampling chamber, saidcatheter being left disposed at the sampling site for a predeterminedlength of time sufficient to allow any of said fluids of interestpresent at the wall portion of the organ sampling site to permeateacross the wall of said sampling chamber into said sampling chamber; andmeans for withdrawing at least a portion of said diffused fluids ofinterest.